The Molecular Control Center of Our Protein Factories
Published:07 Sep.2023    Source:University of Konstanz

Based on genetic blueprints, individual amino acids are assembled into long amino acid chains, the proteins, in the protein factories of our cells, the ribosomes. Each newly formed protein starts with the amino acid methionine. This amino acid is often split off again during protein synthesis, as soon as the growing amino acid chain leaves the protein factory through the "ribosomal tunnel." In these cases, the excision of methionine is essential to ensure the subsequent function of the corresponding proteins in the cell.

The enzymes causing this cleavage are already known. According to their function, they are called methionine aminopeptidases (METAPs). Up to now, it was unclear how METAPs come into contact with the protein factories and, just at the right place and moment, cause the excision of methionine from specific proteins. Biologists Elke Deuerling, Martin Gamerdinger, Nenad Ban and their team found that access of METAPs to protein factories is controlled by a "ribosomal gatekeeper" called NAC (short for "nascent polypeptide-associated complex").
NAC sits in front of the tunnel exit like a gatekeeper. There it controls the transport of proteins to the endoplasmic reticulum (ER) -- the membrane network inside the cell -- by specifically bringing together protein and transport molecule (SRP). Methionine excision in these proteins would destroy the signal and thus prevent its transport into the cell's membrane network, which would inevitably lead to cell death. This mechanism means that proteins lacking signal sequences can be specifically modified by methionine excision. Those, in contrast, that are transported to the endoplasmic reticulum, remain unaffected by METAP1. There is a large number of enzymes and transport molecules that, like METAP1 and SRP, interact with the nascent proteins already during protein synthesis. Future studies will therefore have to show whether NAC also plays a role in regulating other processes that are vital for the function of cells